Libya's state news agency says gunmen have stolen $54m (£33.5m) in an attack on a van carrying foreign and local currency for the Libyan central bank.
"The robbery is a catastrophe for the whole of Libya," Abdel-Fattah Mohammed, head of Sirte council, told Reuters.
Libya has suffered continuing lawlessness since the 2011 civil war.
Guards 'overpowered' Libya's government has been struggling to keep control of a country full of armed militias, gangs and radical Islamists.
Reports on Monday suggested that only one security vehicle had been assigned to protect the van.
Security guards "were unable to resist the 10 attackers", the Lana news agency reported.
Some 53m Libyan dinars were taken, along with another $12m in US dollars and euros.
Two banks in Sirte were hit by robbers in July, a city official told the AFP news agency.
The attackers made off with 500,000 Libyan dinars, he said.
Sirte was the last bastion of support for Col Muammar Gaddafi in the conflict that led to his overthrow.
However the city has largely been spared the wave of violence that has swept since then.